The Yale Mouse Metabolic Phenotyping Center (MMPC) was established in 2000 with the mission to advance research in the area of diabetes by providing novel experimental tools to the scientific community for phenotyping mouse transgenic models of diabetes and related disorders. The goals of this program are to: 1) broaden the scope of techniques available to investigators; 2) standardize key methodologies; 3) expedite completion of research; and 4) compile and make accessible phenotyping data to the scientific community, and 5) develop novel methodology for phenotyping transgenic mice through a nationally administered Pilot & Feasibility Program. The cornerstone of the Yale MMPC is its two research cores; The Integrative Physiology Core and the Metabolomics Core. The Integrative Physiology Core performs glucose-insulin clamps using radioactive and stable isotope tracers to assess insulin action in liver, skeletal muscle, and fat of awake mice. This core also performs hyperglycemic clamps to assess in vivo ?-cell function as well as hypoglycemic clamps to assess complications relating to defective glucose counter-regulation. This core also performs 24- hour, automated, non-invasive assessment of activity, food/water consumption and energy expenditure in an environmentally controlled room. The BioImaging Sub-Core performs noninvasive measurements of metabolites in muscle, liver and brain using 13C/31P/1H MRS, which in turn is used to assess in vivo metabolic flux through critical biochemical pathways as well as whole body composition measurements with MRI. The Islet Biology Sub-Core determines rates of stimulated insulin secretion from isolated islets, and uses stable isotope tracers and LC-MS/MS to quantify metabolic fluxes that regulate insulin secretion. The Metabolomics Core provides clinical chemistry analyses of mouse plasma and urine, and GC-MS, LC-MS/MS, and NMR analysis of mouse plasma, urine and tissue samples. The Microbiome and Animal Care Core provides a centralized facility for coordinating the import, quarantine, screening and monitoring of mice. This Core provides stable, biocontainment housing, husbandry and health care for mice submitted to the Center and determines the microbiological profile of each imported cohort. A newly developed Microbiome component of this core provides a gnotobiotic mouse suite which supports the breeding and maintenance of germfree mouse lines, fecal microbiome transplantation, and provides compositional profiling and metagenomic characterization of the gut microbiome. The Administrative Core oversees operation of the Center, coordinates importation of mice, performs all material transfer agreements, coordinates and schedules meetings and teleconferences between investigators and MMPC Core Directors, coordinates the P&F Program, and administers the Enrichment Program. Overall the Yale MMPC serves as a national research center that provides investigators both inside and outside Yale access to unique, state-of-the-art, standardized methods to further characterize their novel transgenic mouse models of complex metabolic diseases in a cost efficient manner.